Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells

Abstract

Purpose Prostate tumor cells frequently show the features of osteoblasts, which are differentiated from bone marrow mesenchymal stem cells. We examined human prostate cancer cell lines and clinical prostate cancer specimens for additional bone marrow mesenchymal stem cell properties. Experimental Design Prostate cancer cell lines were induced for osteoblastogenic and adipogenic differentiation, detected by standard staining methods and confirmed by lineage-specific marker expression. Abnormal expression of the markers was then assessed in clinical prostate cancer specimens. Results After osteoblastogenic induction, cells of the LNCaP lineage, PC-3 lineage and DU145 displayed osteoblastic features. Upon adipogenic induction, PC-3 lineage and DU145 cells differentiated into adipocyte-like cells. The adipocyte-like cancer cells expressed brown adipocyte-specific markers, suggesting differentiation along the brown adipocyte lineage. The adipogenic differentiation was accompanied by growth inhibition, and most of the adipocyte-like cancer cells were committed to apoptotic death. During cyclic treatments with adipogenic differentiation medium and then with control medium, the cancer cells could commit to repeated adipogenic differentiation and retrodifferentiation. In clinical prostate cancer specimens, the expression of UCP1, a brown fat-specific marker, was enhanced with the level of expression correlated to disease progression from primary to bone metastatic cancers. Conclusions This study thus revealed that prostate cancer cells harbor the stem cell properties of bone marrow mesenchymal stem cells. The abnormally expressed adipogenic UCP1 protein may serve as a unique marker, while adipogenic induction can be explored as a differentiation therapy for prostate cancer progression and bone metastasis.

Human ovarian carcinoma–associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production

“…One study demonstrated that prostate cancer cell lines had the ability to differentiate into osteoblasts and brown adipose. The ability of primary prostate tumor cells to differentiate was not assessed (55). A second study in ovarian cancer suggested that primary CD133 + EpCAM + CD44 + ovarian CSCs, after passage in mice, could produce mesenchymal cells in vitro (56).…”

Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors

“…More recently, the differentiation potential of prostate cancer cells to assume an adipocyte lineage phenotype was revealed. 27 Human prostate cancer cell lines PC3 and DU145 reversibly differentiate into an adipocyte-like phenotype in vitro under adipogenic induction conditions, leading to growth arrest and apoptosis. 27 Similarly, human prostate cancer bone metastatic tissue microarray (TMA) samples exhibit a brown fatspecific marker, UCP1, suggesting that prostate cancer cells may also differentiate into an adipocyte phenotype in vivo.…”

“…27 Human prostate cancer cell lines PC3 and DU145 reversibly differentiate into an adipocyte-like phenotype in vitro under adipogenic induction conditions, leading to growth arrest and apoptosis. 27 Similarly, human prostate cancer bone metastatic tissue microarray (TMA) samples exhibit a brown fatspecific marker, UCP1, suggesting that prostate cancer cells may also differentiate into an adipocyte phenotype in vivo. 27 As the differentiation potential of prostate cancer is likened to that of MSCs, 27 it is also possible that disseminated prostate cancer acquires an MSC-like phenotype to colonize the bone marrow.…”

Development of a Novel Method to Detect Prostate Cancer Circulating Tumor Cells (CTCs) Based on Epithelial-Mesenchymal Transition Biology

“…The upregulation of β2-microglobulin, an immune regulator protein, can induce EMT, promote osteomimicry, and lead to bone metastasis in mouse models of prostate and other cancers [31]. Furthermore, PC cell lines can be forced to differentiate into osteoblast-like cells or adipose cells [32], suggesting that PC cells have the inherent capability to change phenotypes. Additional studies have established that PC cells produce soluble factors that lead to the expression of osteoblast-specific genes [33].…”